RESUMO
BACKGROUND AND PURPOSE: Morning glory disc anomaly (MGDA) is a congenital malformation characterized by a funnel-shaped optic disc excavation with radiating vessels and a central glial tuft. Imaging is essential to evaluate associated cephalocele and steno-occlusive vasculopathy. The goal of this study was to assess optic nerve, chiasmatic, and sphenoid bone morphology in MGDA. MATERIALS AND METHODS: This retrospective study examined all subjects with funduscopically confirmed MGDA diagnosed and imaged with brain MR imaging between 2008 and 2023. RESULTS: Thirty-two children met inclusion criteria. Ocular involvement was unilateral in 29 subjects and bilateral in 3. Segmental optic nerve enlargement ipsilateral to the MGDA was seen in 21 subjects, with 3 also demonstrating a segmental reduction in the size of the ipsilateral optic nerve. Segmental reduction in the size of the ipsilateral optic nerve was present in 3 additional subjects, one with bilateral MGDA. The optic chiasm appeared asymmetrically thickened in 21 subjects, often with deformity. The optic nerves appeared normal in signal intensity in all subjects, with faint peripheral chiasmatic enhancement in 4 of 20 patients who received contrast. Optic nerve findings were stable in 15 subjects with multiple examinations. A persistent craniopharyngeal canal was identified in 17 subjects with sphenoid cephalocele in 1 and mild inferior pituitary gland displacement in 4. Tubular or nodular nasopharyngeal lesions were seen in 10 subjects. One subject had an off-midline sphenoid bone cleft, midbrain deformity, and abnormal thickening of and enhancement around the left oculomotor nerve; the oculomotor nerve finding was present in 1 additional patient. CONCLUSIONS: MGDA often manifests with ipsilateral optic nerve thickening, leading to a potential misdiagnosis as optic glioma. MGDA is also commonly associated with a persistent craniopharyngeal canal with variable pituitary gland and infundibular deformity, cephalocele, and tubular or nodular nasopharyngeal lesions.
Assuntos
Imageamento por Ressonância Magnética , Disco Óptico , Humanos , Feminino , Masculino , Estudos Retrospectivos , Criança , Imageamento por Ressonância Magnética/métodos , Disco Óptico/diagnóstico por imagem , Disco Óptico/anormalidades , Disco Óptico/patologia , Pré-Escolar , Adolescente , Lactente , Fenótipo , Osso Esfenoide/diagnóstico por imagem , Osso Esfenoide/anormalidades , Osso Esfenoide/patologia , Quiasma Óptico/diagnóstico por imagem , Quiasma Óptico/anormalidades , Quiasma Óptico/patologia , Anormalidades do Olho/diagnóstico por imagem , Anormalidades do Olho/patologiaRESUMO
We describe a collection of T1-, diffusion- and functional T2*-weighted magnetic resonance imaging data from human individuals with albinism and achiasma. This repository can be used as a test-bed to develop and validate tractography methods like diffusion-signal modeling and fiber tracking as well as to investigate the properties of the human visual system in individuals with congenital abnormalities. The MRI data is provided together with tools and files allowing for its preprocessing and analysis, along with the data derivatives such as manually curated masks and regions of interest for performing tractography.
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Albinismo/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Quiasma Óptico/anormalidades , Anormalidades Congênitas/diagnóstico por imagem , Humanos , Quiasma Óptico/diagnóstico por imagemRESUMO
Circadian rhythm is usually regulated by the environmental light-dark cycle. Congenitally anophthalmic miniature pigs provide a valuable model for the study of factors affecting circadian rhythms in the absence of visual exposure to the light-dark cycle. This study investigated the growth and daily behavior patterns of Lee-Sung pigs with congenital anophthalmia. Growth in 5 Lee-Sung pigs (LSP) with congenital anophthalmia (LSP-A) and 10 normally developed pigs (LSP-N) was assessed when they were 1 through 6 mo old. Behavioral studies using digital video recording were completed in 6 sexually mature LSP (3 LSP-A and 3 LSP-N). MRI showed that LSP-A lose their vision because of a lack of retinal input and optic chiasm development. LSP-N and LSP-A did not differ in body weight or size at 2, 4, and 6 mo of age. Behavior and activity pattern studies showed that both LSP-A and LSP-N were active mainly during daylight, but LSP-A spent significantly more time exploring their environment during the day (28%) and night (10%) than did LSP-N. This study revealed that growth performance was similar between LSP-A and normal pigs, but their behavior and activity patterns differed. LSP-A showed circadian rhythm abnormalities similar to those in blind humans. This study provides basic data on LSP-A as a model for studying compensatory cross-modal brain plasticity and hormone regulation in the absence of retinal input is deficient and for understanding the role of circadian rhythm regulation.
Assuntos
Anoftalmia/veterinária , Doenças dos Suínos/congênito , Porco Miniatura/anormalidades , Animais , Anoftalmia/diagnóstico por imagem , Anoftalmia/fisiopatologia , Comportamento Animal , Cegueira/fisiopatologia , Encéfalo/diagnóstico por imagem , Ritmo Circadiano , Modelos Animais de Doenças , Humanos , Imageamento por Ressonância Magnética , Atividade Motora , Quiasma Óptico/anormalidades , Quiasma Óptico/diagnóstico por imagem , Nervo Óptico/anormalidades , Nervo Óptico/diagnóstico por imagem , Suínos , Doenças dos Suínos/diagnóstico por imagem , Doenças dos Suínos/fisiopatologia , Porco Miniatura/crescimento & desenvolvimento , Porco Miniatura/fisiologiaRESUMO
A fundamental scheme in the organization of the early visual cortex is the retinotopic representation of the contralateral visual hemifield on each hemisphere. We determined the cortical organization in a novel congenital visual pathway disorder, FHONDA-syndrome, where the axons from the temporal retina abnormally cross to the contralateral hemisphere. Using ultra-high field fMRI at 7â¯T, the population receptive field (pRF) properties of the primary visual cortex were modeled for two affected individuals and two controls. The cortical activation in FHONDA was confined to the hemisphere contralateral to the stimulated eye. Each cortical location was found to contain a pRF in each visual hemifeld and opposing hemifields were represented as retinotopic cortical overlays of mirror-symmetrical locations across the vertical meridian. Since, the enhanced crossing of the retinal fibers at the optic chiasm observed in FHONDA has been previously assumed to be exclusive to the pigment-deficiency in albinism, our direct evidence of abnormal mapping in FHONDA highlights the independence of pigmentation and development of the visual cortex. These findings thus provide fundamental insights into the developmental mechanisms of the human visual system and underline the general relevance of the interplay of subcortical stability and cortical plasticity.
Assuntos
Segmento Anterior do Olho/anormalidades , Anormalidades do Olho/fisiopatologia , Fóvea Central/anormalidades , Plasticidade Neuronal/fisiologia , Quiasma Óptico/anormalidades , Nervo Óptico/anormalidades , Córtex Visual/fisiopatologia , Campos Visuais/fisiologia , Vias Visuais/anormalidades , Percepção Visual/fisiologia , Adulto , Segmento Anterior do Olho/diagnóstico por imagem , Segmento Anterior do Olho/fisiopatologia , Mapeamento Encefálico , Anormalidades do Olho/diagnóstico por imagem , Feminino , Fóvea Central/diagnóstico por imagem , Fóvea Central/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Estimulação Luminosa , Córtex Visual/diagnóstico por imagemRESUMO
PURPOSE: To describe the phenotypic spectrum of a large cohort of albino patients, to investigate the relationship between the ocular abnormalities and the visual acuity (VA), and to define diagnostic criteria for the white population. We also estimated the prevalence of albinism in The Netherlands. DESIGN: Retrospective cohort study. PARTICIPANTS: We investigated the phenotype of 522 patients with albinism from the databases of Bartiméus (452 patients), Leiden University Medical Center (44 patients), and the Academic Medical Center Amsterdam (26 patients). METHODS: We collected clinical, genetic, and electrophysiologic data of patients with albinism. We used grading schemes for iris translucency, fundus hypopigmentation, and foveal hypoplasia. MAIN OUTCOME MEASURES: Visual acuity, nystagmus, iris translucency, fundus pigmentation, foveal hypoplasia, and misrouting. RESULTS: Nystagmus was absent in 7.7% (40/521), iris translucency could not be detected in 8.9% (44/492), 3.8% (19/496) had completely normal fundus pigmentation, 0.7% (3/455) had no foveal hypoplasia, and misrouting was not established in 16.1% (49/304). The VA varied from -0.1 to 1.3 logarithm of the minimum of angle of resolution (logMAR). The foveal hypoplasia grading correlated best with the VA (r = 0.69, P < 0.001), whereas iris translucency, fundus pigmentation, and misrouting did not predict the VA significantly. We estimated a prevalence of albinism in The Netherlands of at least 1:12 000. CONCLUSIONS: None of the characteristics of albinism were consistently present in our cohort. To be able to distinguish albinism from other conditions with similar ocular features, especially in northern and western European countries, we propose major and minor clinical criteria. Major criteria would be (1) foveal hypoplasia grade 2 or more, (2) misrouting, and (3) ocular hypopigmentation, either iris translucency or fundus hypopigmentation grade 2 or more. Minor criteria would be (1) nystagmus, (2) hypopigmentation of skin and hair, (3) grade 1 fundus hypopigmentation, and (4) foveal hypoplasia grade 1. We propose that 3 major criteria or 2 major and 2 minor criteria are necessary for the diagnosis. In the presence of a molecular diagnosis, 1 major criterion or 2 minor criteria will be sufficient.
Assuntos
Albinismo Oculocutâneo/diagnóstico , Fóvea Central/anormalidades , Doenças da Íris/diagnóstico , Nistagmo Patológico/diagnóstico , Transtornos da Visão/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Potenciais Evocados Visuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Quiasma Óptico/anormalidades , Doenças do Nervo Óptico/diagnóstico , Fenótipo , Estudos Retrospectivos , Acuidade VisualAssuntos
Fibras Nervosas/patologia , Nistagmo Patológico/patologia , Quiasma Óptico/anormalidades , Quiasma Óptico/patologia , Vias Visuais/patologia , Feminino , Humanos , Lactente , Nistagmo Patológico/complicações , Nistagmo Patológico/diagnóstico por imagem , Quiasma Óptico/diagnóstico por imagem , Vias Visuais/diagnóstico por imagemRESUMO
In evaluating a 3-month-old boy with horizontal nystagmus, brain MRI revealed absence of the optic chiasm. The remainder of the brain was normal in appearance. Achiasma was confirmed with diffusion tensor imaging and best visualized with optimized probabilistic-based tractography.
Assuntos
Quiasma Óptico/anormalidades , Doenças do Nervo Óptico/congênito , Acuidade Visual , Imagem de Difusão por Ressonância Magnética/métodos , Seguimentos , Humanos , Lactente , Masculino , Quiasma Óptico/diagnóstico por imagem , Doenças do Nervo Óptico/diagnósticoRESUMO
In the absence of an optic chiasm, visual input to the right eye is represented in primary visual cortex (V1) in the right hemisphere, while visual input to the left eye activates V1 in the left hemisphere. Retinotopic mapping In V1 reveals that in each hemisphere left and right visual hemifield representations are overlaid (Hoffmann et al., 2012). To explain how overlapping hemifield representations in V1 do not impair vision, we tested the hypothesis that visual projections from nasal and temporal retina create interdigitated left and right visual hemifield representations in V1, similar to the ocular dominance columns observed in neurotypical subjects (Victor et al., 2000). We used high-resolution fMRI at 7T to measure the spatial distribution of responses to left- and right-hemifield stimulation in one achiasmic subject. T2-weighted 2D Spin Echo images were acquired at 0.8mm isotropic resolution. The left eye was occluded. To the right eye, a presentation of flickering checkerboards alternated between the left and right visual fields in a blocked stimulus design. The participant performed a demanding orientation-discrimination task at fixation. A general linear model was used to estimate the preference of voxels in V1 to left- and right-hemifield stimulation. The spatial distribution of voxels with significant preference for each hemifield showed interdigitated clusters which densely packed V1 in the right hemisphere. The spatial distribution of hemifield-preference voxels in the achiasmic subject was stable between two days of testing and comparable in scale to that of human ocular dominance columns. These results are the first in vivo evidence showing that visual hemifield representations interdigitate in achiasmic V1 following a similar developmental course to that of ocular dominance columns in V1 with intact optic chiasm.
Assuntos
Mapeamento Encefálico/métodos , Dominância Ocular/fisiologia , Quiasma Óptico/anormalidades , Quiasma Óptico/diagnóstico por imagem , Córtex Visual/diagnóstico por imagem , Adulto , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , MasculinoRESUMO
PURPOSE: To demonstrate the utility of an uncrossed asymmetry in full-field pattern reversal visual evoked potentials (FF-PVEPs) will accurately predict a retrochiasmal lesion confirmed by MRI. METHODS: During an 8-year period, 754 patients had FF-PVEPs performed and analyzed without knowledge of their clinical histories and imaging studies. Interhemispheric amplitude ratios were calculated between N75-P100 and P100-N145 and deemed significant if both demonstrated greater than 50% amplitude asymmetry no matter which eye was stimulated (uncrossed symmetry). RESULTS: We identified 11 patients of 754 patients evaluated for 8 years (1.5%) whose FF-PVEP fulfilled our amplitude criteria. Ten of 11 had retrochiasmal lesions confirmed with MRI for a calculated positive predictive value of 91%. CONCLUSIONS: These data provide initial support for the hypothesis that specified amplitude criteria in FF-PVEPs can provide evidence for a retrochiasmal lesion. An abnormal interhemispheric amplitude ratio in FF-PVEPs is underrecognized as a diagnostic criterion for retrochiasmal lesion prediction.
Assuntos
Eletroencefalografia , Potenciais Evocados Visuais/fisiologia , Quiasma Óptico/anormalidades , Quiasma Óptico/fisiopatologia , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Exame Neurológico , Quiasma Óptico/diagnóstico por imagem , Estudos Retrospectivos , Vias Visuais/fisiopatologiaRESUMO
We report the clinical details and imaging findings for a case of nondecussating retinal-fugal fiber syndrome or isolated achiasma in a 4-year-old female child. Findings included the isolated absence of optic chiasm with unremarkable rest of the optic pathway and midline structures in a child presenting clinically with see-saw nystagmus. Clinically congenital see-saw nystagmus, "mirror reversal" of visual field representation and interocular ipsilateral asymmetry on monocular visual evoked potential point toward achiasma and warrant further evaluation with magnetic resonance imaging (MRI). Isolated achiasma is a rare condition that may remain undiagnosed unless MRI is done.
Assuntos
Anormalidades do Olho/diagnóstico por imagem , Imageamento por Ressonância Magnética , Fibras Nervosas/patologia , Nistagmo Congênito/diagnóstico por imagem , Quiasma Óptico/anormalidades , Células Ganglionares da Retina/patologia , Vias Visuais/anormalidades , Pré-Escolar , Feminino , HumanosRESUMO
No disponible
Assuntos
Humanos , Masculino , Feminino , Quiasma Óptico/anatomia & histologia , Quiasma Óptico/patologia , Anatomia/história , Quiasma Óptico/anormalidades , História , Fisiologia/históriaRESUMO
Optic nerve (ON) aplasia is a rare developmental anomaly comprising of absence of the ON, ganglion cells and the central retinal vessels. It is usually accompanied by a variety of central nervous system (CNS) malformations. We report an extremely rare case of bilateral true ON aplasia occurring as an isolated CNS anomaly. A 10-month-old female child was detected with bilateral absence of fixation, associated with multiple ocular findings of microcornea, anterior embryotoxon, pupillary corectopia, partial aniridia and lens coloboma. The optic disc locations were visible as avascular whitish areas. There were no retinal vessels seen in the disc area or elsewhere. There were bilateral multiple chorioretinal atrophic patches present. B-scan ultrasonography showed bilateral absence of ONs. Magnetic resonance imaging showed thinned out bilateral ONs with a hypoplastic optic chiasma and optic tract. There were no other CNS anomalies. Flash visually evoked potential was unrecordable.
Assuntos
Disco Óptico/anormalidades , Doenças do Nervo Óptico/diagnóstico , Vasos Retinianos/anormalidades , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Quiasma Óptico/anormalidadesRESUMO
BACKGROUND AND METHODS: In routine clinical evaluation of optic neuritis and chiasmal tumours, pattern electroretinography and visual evoked potentials (VEPs) to pattern-reversal stimulation are useful examinations. Similarly, in achiasmia and ocular albinism, VEPs to flash and pattern-onset stimulation provide relevant information. RESULTS: The role of visual electrophysiology in these diseases is to assess potential dysfunction of the visual pathway: (a) at the acute stage of optic neuritis, to determine the magnitude of conduction block of the optic nerve fibres; (b) at the clinical recovery stage of optic neuritis, to determine optic nerve conduction delay due to demyelination, and to follow possible remyelination; (c) at the recovery of optic neuritis when visual acuity does not normalise, to define loss of optic nerve fibres and retrograde degeneration of retinal ganglion cells; (d) in tumours at the chiasm, to detect abnormal conduction along the crossed and/or uncrossed fibres; and (e) in achiasmia or albinism, which are both congenital disorders associated with nystagmus, to detect achiasmia and absence of or reduced optic nerve fibre decussation at the chiasm, or to detect ocular albinism and excess of optic nerve fibre decussation at the chiasm. In optic neuritis, two recent examinations have been used to detect retrograde axonal degeneration: photopic negative response of the electroretinogram, to assess dysfunction of ganglion cell axons; and optic coherence tomography, to measure thinning of the retinal nerve fibre layer. In optic neuritis, multifocal VEPs provide a promising clinical examination, because this can show areas that are associated with normal or abnormal optic nerve fibre function. CONCLUSIONS: Visual electrophysiology defines function of the visual pathway and is relevant: (1) in optic neuritis, when visual acuity does not recover well; (2) in tumours of the chiasm with normal visual fields, as in paediatric patients who cannot adequately perform perimetry; and (3) in children with congenital nystagmus and suspected achiasmia or ocular albinism.
Assuntos
Albinismo Ocular/diagnóstico , Eletrofisiologia/métodos , Anormalidades do Olho/diagnóstico , Quiasma Óptico/patologia , Neoplasias do Nervo Óptico/diagnóstico , Neurite Óptica/diagnóstico , Eletrorretinografia , Potenciais Evocados Visuais , Humanos , Quiasma Óptico/anormalidadesAssuntos
Atresia Esofágica/diagnóstico , Microftalmia/diagnóstico , Malformações do Sistema Nervoso/diagnóstico , Encaminhamento e Consulta , Deleção Cromossômica , Atresia Esofágica/genética , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Microftalmia/genética , Mutação/genética , Malformações do Sistema Nervoso/genética , Quiasma Óptico/anormalidades , Nervo Óptico/anormalidades , Fatores de Transcrição SOXB1/genéticaRESUMO
PURPOSE: We have previously described two families with unique phenotypes involving foveal hypoplasia. The first family (F1) presented with foveal hypoplasia and anterior segment dysgenesis, and the second family (F2) presented with foveal hypoplasia and chiasmal misrouting in the absence of albinism. A genome-wide linkage search in family F1 identified a 6.5 Mb locus for this disorder on chromosome 16q23.2-24.1. The aim of this study was to determine if both families have the same disorder and to see if family F2 is also linked to the 16q locus. METHODS: Family members underwent routine clinical examination. Linkage was determined by genotyping microsatellite makers and calculating logarithm of the odds (LOD) scores. Locus refinement was undertaken with single nucleotide polymorphism (SNP) microarray analysis. RESULTS: The identification of chiasmal misrouting in family F1 and anterior segment abnormalities in family F2 suggested that the families have the same clinical phenotype. This was confirmed when linkage analysis showed that family F2 also mapped to the 16q locus. The single nucleotide polymorphism microarray analysis excluded a shared founder haplotype between the families and refined the locus to 3.1 Mb. CONCLUSIONS: We report a new recessively inherited syndrome consisting of foveal hypoplasia, optic nerve decussation defects and anterior segment dysgenesis, which we have abbreviated to FHONDA syndrome. The gene mutated in this disorder lies within a 3.1 Mb interval containing 33 genes on chromosome 16q23.3-24.1 (chr16:83639061 - 86716445, hg19).
Assuntos
Segmento Anterior do Olho/anormalidades , Cromossomos Humanos Par 16/genética , Fóvea Central/anormalidades , Genes Recessivos/genética , Padrões de Herança/genética , Quiasma Óptico/anormalidades , Nervo Óptico/anormalidades , Adolescente , Segmento Anterior do Olho/patologia , Criança , Mapeamento Cromossômico , Família , Feminino , Fóvea Central/patologia , Ligação Genética , Genótipo , Humanos , Masculino , Quiasma Óptico/patologia , LinhagemRESUMO
The major active retinoid, all-trans retinoic acid, has long been recognized as critical for the development of several organs, including the eye. Mutations in STRA6, the gene encoding the cellular receptor for vitamin A, in patients with Matthew-Wood syndrome and anophthalmia/microphthalmia (A/M), have previously demonstrated the importance of retinol metabolism in human eye disease. We used homozygosity mapping combined with next-generation sequencing to interrogate patients with anophthalmia and microphthalmia for new causative genes. We used whole-exome and whole-genome sequencing to study a family with two affected brothers with bilateral A/M and a simplex case with bilateral anophthalmia and hypoplasia of the optic nerve and optic chiasm. Analysis of novel sequence variants revealed homozygosity for two nonsense mutations in ALDH1A3, c.568A>G, predicting p.Lys190*, in the familial cases, and c.1165A>T, predicting p.Lys389*, in the simplex case. Both mutations predict nonsense-mediated decay and complete loss of function. We performed antisense morpholino (MO) studies in Danio rerio to characterize the developmental effects of loss of Aldh1a3 function. MO-injected larvae showed a significant reduction in eye size, and aberrant axonal projections to the tectum were noted. We conclude that ALDH1A3 loss of function causes anophthalmia and aberrant eye development in humans and in animal model systems.
Assuntos
Aldeído Oxirredutases/genética , Anoftalmia/genética , Códon sem Sentido/genética , Microftalmia/genética , Quiasma Óptico/anormalidades , Nervo Óptico/anormalidades , Aldeído Oxirredutases/metabolismo , Animais , Anoftalmia/metabolismo , Criança , Pré-Escolar , Exoma , Olho/crescimento & desenvolvimento , Olho/patologia , Feminino , Genoma , Homozigoto , Humanos , Lactente , Larva/genética , Larva/crescimento & desenvolvimento , Larva/metabolismo , Masculino , Microftalmia/metabolismo , Análise de Sequência de DNA , Análise de Sequência de RNA , Peixe-Zebra/embriologia , Peixe-Zebra/genéticaRESUMO
OBJECTIVE: To examine the anatomic features and function of the macula in achiasma and to compare visual acuity, eye movements, foveation, and eye velocity before and after tenotomy and reattachment (T&R) surgery. DESIGN: Case series. PARTICIPANTS: Two children with isolated achiasma. METHODS: Ophthalmologic examinations, brain magnetic resonance imaging, full-field and multifocal electroretinography (ERG), visual evoked potentials (VEPs), spectral-domain optical coherence tomography (OCT), eye-movement recordings, and unilateral T&R in 1 patient. MAIN OUTCOME MEASURES: Visual acuity before and after surgery, macular anatomic features and function, and eye velocity before and after T&R surgery in 1 patient. RESULTS: Magnetic resonance imaging and VEP confirmed absence of decussation of retinofugal fibers in both patients. Visual acuity was 20/100 and 20/200. The anatomic features and function of the fovea and macula were normal by OCT and multifocal ERG. After T&R, there was a marked reduction in horizontal eye velocity and monocular visual acuity improved to 20/80. CONCLUSIONS: The finding that the macula is normal in achiasma suggests that reduced acuity is the result of retinal image motion from nystagmus. Two-muscle T&R reduces horizontal retinal image motion and can improve visual acuity in achiasma or patients with infantile nystagmus.
Assuntos
Macula Lutea/fisiopatologia , Nistagmo Congênito/fisiopatologia , Quiasma Óptico/anormalidades , Quiasma Óptico/cirurgia , Tenotomia , Criança , Pré-Escolar , Eletrorretinografia , Potenciais Evocados Visuais/fisiologia , Movimentos Oculares/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Quiasma Óptico/fisiopatologia , Estudos Retrospectivos , Tomografia de Coerência Óptica , Visão Binocular/fisiologia , Acuidade Visual/fisiologia , Campos Visuais/fisiologia , Vias Visuais/fisiopatologiaRESUMO
BACKGROUND: Previous studies have suggested that the axon guidance proteins Slit1 and Slit2 co-operate to establish the optic chiasm in its correct position at the ventral diencephalic midline. This is based on the observation that, although both Slit1 and Slit2 are expressed around the ventral midline, mice defective in either gene alone exhibit few or no axon guidance defects at the optic chiasm whereas embryos lacking both Slit1 and Slit2 develop a large additional chiasm anterior to the chiasm's normal position. Here we used steerable-filters to quantify key properties of the population of axons at the chiasm in wild-type, Slit1(-/-), Slit2(-/-) and Slit1(-/-)Slit2(-/-) embryos. RESULTS: We applied the steerable-filter algorithm successfully to images of embryonic retinal axons labelled from a single eye shortly after they have crossed the midline. We combined data from multiple embryos of the same genotype and made statistical comparisons of axonal distributions, orientations and curvatures between genotype groups. We compared data from the analysis of axons with data on the expression of Slit1 and Slit2. The results showed a misorientation and a corresponding anterior shift in the position of many axons at the chiasm of both Slit2(-/-) and Slit1(-/-)Slit2(-/-) mutants. There were very few axon defects at the chiasm of Slit1(-/-) mutants. CONCLUSIONS: We found defects of the chiasms of Slit1(-/-)Slit2(-/-) and Slit1(-/-) mutants similar to those reported previously. In addition, we discovered previously unreported defects resulting from loss of Slit2 alone. This indicates the value of a quantitative approach to complex pathway analysis and shows that Slit2 can act alone to control aspects of retinal axon routing across the ventral diencephalic midline.
Assuntos
Axônios/fisiologia , Padronização Corporal/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Peptídeos e Proteínas de Sinalização Intercelular/deficiência , Proteínas do Tecido Nervoso/deficiência , Quiasma Óptico , Animais , Carbocianinas , Embrião de Mamíferos , Filtração/instrumentação , Filtração/métodos , Genótipo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Camundongos , Camundongos Knockout , Proteínas do Tecido Nervoso/genética , Quiasma Óptico/anormalidades , Quiasma Óptico/embriologia , Quiasma Óptico/metabolismo , Vias Visuais/embriologia , Vias Visuais/metabolismoRESUMO
The absence of the optic chiasm is an extraordinary and extreme abnormality in the nervous system. The abnormality produces highly atypical functional responses in the cortex, including overlapping hemifield representations and bilateral population receptive fields in both striate and extrastriate visual cortex. Even in the presence of these large functional abnormalities, the effect on visual perception and daily life is not easily detected. Here, we demonstrate that in two achiasmic humans the gross topography of the geniculostriate and occipital callosal connections remains largely unaltered. We conclude that visual function is preserved by reorganization of intracortical connections instead of large-scale reorganizations of the visual cortex. Thus, developmental mechanisms of local wiring within cortical maps compensate for the improper gross wiring to preserve function in human achiasma.